Archive for May, 2009

University of Hawaii at Manoa professors co-author adolescent obesity study

Drs. Timothy Halliday and Sally Kwak, economics professors at the University of Hawaii at Manoa, recently published a paper in Economics and Human Biology titled, “Weight Gain in Adolescents and Their Peers.” The article examines trends in adolescent body mass index (BMI) in a nationally representative dataset.

In their study, Halliday and Kwak document strong correlations in weight gain between adolescents and their friends, even after controlling for confounding factors such as race, sex and age. While these correlations may be indicative of pupils causing their peers to gain weight, the authors provide evidence that a substantial part of the correlations is a consequence of sorting on BMI.

In addition, they discuss many of the econometric issues in estimating such effects while accounting for growth spurts and difficulties in defining adolescent obesity. Halliday and Kwak discuss policy implications of such findings for school-based interventions to combat obesity. Their work contributes to a growing body of literature studying the impact of peers on student outcomes.

Source: University of Hawaii at Manoa

Following a healthy lifestyle is on the decline in the US

New York, NY, May 27, 2009 – Despite the well-known benefits of having a lifestyle that includes physical activity, eating a diet high in fruits and vegetables, maintaining a healthy weight, moderate alcohol use and not smoking, only a small proportion of adults follow this healthy lifestyle pattern, and in fact, the numbers are declining, according to an article published in the June 2009 issue of The American Journal of Medicine. Lifestyle choices are associated with the risk of cardiovascular disease as well as diabetes.

Investigators from the Department of Family Medicine, Medical University of South Carolina, Charleston compared the results of two large-scale studies of the US population in 1988-1994 and in 2001-2006. In the intervening 18 years, the percentage of adults aged 40-74 years with a body mass index greater than 30 has increased from 28% to 36%; physical activity 12 times a month or more has decreased from 53% to 43%; smoking rates have not changed (26.9% to 26.1%); eating 5 or more fruits and vegetables a day has decreased from 42% to 26%; and moderate alcohol use has increased from 40% to 51%. The number of people adhering to all 5 healthy habits has decreased from 15% to 8%.

The National Health and Nutrition Examination Survey (NHANES) is a national survey of non-institutionalized persons in the US conducted regularly by the National Center for Health Statistics. The researchers used data from a sub sample of the NHANES surveys of 1988-1994 and 2001-2006, adults aged 40-74 years, because this age span is the primary time for initial diagnosis of cardiovascular risk factors and disease. In the NHANES 1988-1994, the number of respondents 40-74 years old was 7340, representing a weighted sample size of 78,794,217. For NHANES 2001-2006, the number of respondents was 7811, for a weighted sample size of 65,476,573.

Since people with diagnosed health conditions such as cardiovascular disease, diabetes, hypertension, or high cholesterol were part of the samples, the researchers sought to determine whether such individuals were adhering to the healthy habits to a greater or lesser degree than people without those conditions, and whether adherence had changed over time. The study also concluded that people with cardiovascular disease, diabetes, high blood pressure or high cholesterol, or risk factors for those conditions, were no more likely to adhere to a healthy lifestyle pattern than people without such risk factors.

Writing in the article, Dana E. King, MD, MS, states, “The potential public health benefits from promoting a healthier lifestyle at all ages, and especially ages 40-74 years, are substantial. Regular physical activity and a prudent diet can reduce the risk of premature death and disability from a variety of conditions including coronary heart disease, and are strongly related to the incidence of obesity. In the US, medical costs due to physical inactivity and its consequences are estimated at $76 billion in 2000 dollars. Research indicates that individuals are capable of adopting healthy habits in middle age, and making an impact on cardiovascular risk.”

Source: Elsevier Health Sciences

Cholesterol-lowering drugs may help prevent stroke recurrence

ST. PAUL, Minn. – People who take cholesterol-lowering drugs called statins after a stroke may be less likely to have another stroke later, according to research published in the May 26, 2009, print issue of Neurology®, the medical journal of the American Academy of Neurology.

Those who take statins after a stroke may also be less likely to die within the next 10 years than those who do not take statins.

“Considering the large burden that stroke carries around the world, these potential benefits of statins are significant,” said study author Sotirios Giannopoulos, MD, DSc, of the University of Ioannina School of Medicine in Greece. “Also, second strokes tend to result in more disability and longer time spent in hospitals than first strokes, so anything that can prevent these recurrent strokes is beneficial.”

The study involved 794 people who had strokes and had health information available for 10 years after the stroke. Researchers looked back at the records to see what factors affected the risk for having a second stroke or dying within 10 years after the stroke.

During that time, 112 people had a second stroke and 224 people died. Those who took statins were 35 percent less likely to have a second stroke and 57 percent less likely to die within 10 years than those who did not take statins.

About eight percent of those on statins had a second stroke, compared to 16 percent of those not taking statins.

Researchers analyzed other risk factors for stroke, such as high blood pressure, diabetes, smoking, and heart problems, but found that statin use was the only factor tied to a reduced risk of recurrent stroke and death.

“It’s possible that effects from the drugs that are separate from their cholesterol-lowering effects are responsible for this result,” Giannopoulos said. “Statins have anti-inflammatory and antioxidative effects and also prevent blood clotting and stabilize plaque in the arteries, so one of these mechanisms may help to prevent recurrent stroke.”

Source: American Academy of Neurology

New direction needed for obesity research, Deakin health expert claims

Most of the current obesity research is not proving helpful in finding solutions to the growing international epidemic, according to a Deakin University public health expert.

Professor Boyd Swinburn believes that research funding would be better directed at testing possible solutions rather than continuing to unpick what is causing the rise in obesity.

“It seems counter intuitive, but knowing the causes or mechanisms for weight gain does not always help with identifying the solutions,” he said.

“For an individual person, we know the causes of weight gain over time include the obesogenic environment, genetic predisposition, and increasing age – none of which can be influenced by the health professional trying to help the person lose weight. At a population level, the commercial drivers which promote our overconsumption of food are unlikely to be reversed by the private sector because there is no commercial gain for the food industry to promote eating fewer calories.

“The twin bottom line is that we need to re-orient our research towards testing potential solutions rather than just better identifying the problem. The most promising approaches for individuals and populations will involve identifying the right set of ‘rules’ or policies which lead to sustainable environmental and behavioural changes.”

Professor Swinburn says that identifying solutions needs specific solutions-oriented research and unfortunately most of the current research into obesity is problem-oriented.

“Interestingly, the solutions that are the most likely to work seem to be ‘rule-based’ solutions,” Professor Swinburn explained.

“For overweight individuals, so long as they can stick to a set of dietary rules which results in a reduced calorie intake, it doesn’t seem to matter what foods are included or excluded. This is why lots of different types of diets which are unrelated to the dietary causes of weight gain can produce weight loss.

“Similarly, at a population level, it is likely that rules or policies are likely to be the most promising for prevention. Education, guidelines, industry self-regulation, and government ads on TV are unlikely to have much influence and stronger policies will be needed.”

Professor Swinburn will be speaking about the causes of the current obesity epidemic and potential solutions today (Thursday 21 May) at the Public Health Association of Australia ACT Branch’s Sax Oration in Canberra.

Sleep Apnea and Type 2 Diabetes

Study finds sleep apnea widely undiagnosed among obese type 2 diabetics

Sleep apnea has long been known to be associated with obesity. But a new study published in the June issue of Diabetes Care finds that the disorder is widely undiagnosed among obese individuals with type 2 diabetes – nearly 87 percent of participants reported symptoms, but were never diagnosed.

For those with untreated sleep apnea, it doesn’t just mean their sleep is disrupted; existing research shows that it can also mean an increased risk of heart disease and stroke.

“The high prevalence of undiagnosed, and therefore, untreated sleep apnea among obese patients with diabetes constitutes a serious public health problem,” said Gary Foster, PhD, lead author and director of the Center for Obesity Research and Education at Temple University.

The new study, called Sleep AHEAD, looked at 306 obese patients with type 2 diabetes already enrolled in the Look AHEAD trial, a 16-site study investigating the long-term health impact of an intensive lifestyle intervention in 5, 145 overweight or obese adults with type 2 diabetes.

Each participant had a sleep study (polysomnogram) that measures various breathing and brain activity during sleep. Participants also filled out a series of questions about symptoms related to sleep (snoring, sleepiness during the day), and had their weight, height, waist and neck circumferences measured.

Researchers found that 86.6 percent of participants had sleep apnea, yet reported never being diagnosed. More than 30 percent of these had between 16 and 20 episodes per hour where they would stop breathing, and 22 percent had more than 30 episodes per hour, considered severe sleep apnea. Most of these also had a larger waist circumference, which researchers found, along with higher BMI, to be significantly associated with sleep apnea.

Obesity has long been known to be associated with sleep apnea, but researchers say that these findings are alarming.

“Doctors who have obese patients with type 2 diabetes need to be aware of the possibility of sleep apnea, even if no symptoms are present, especially in cases where the patient has a high BMI or waist circumference,” said Foster.

Currently, more than half of obese or overweight individuals have diabetes, the seventh leading cause of death in the United States.

Source: Temple University

Vitamin D tied to muscle power in adolescent girls

Chevy Chase, MD—Vitamin D is significantly associated with muscle power and force in adolescent girls, according to a new study accepted for publication in The Endocrine Society’s Journal of Clinical Endocrinology & Metabolism (JCEM).

Although vitamin D is naturally produced in the body through exposure to direct sunlight, vitamin D deficiency has become widely common in the United States. Vitamin D deficiency has been shown to have a significant negative impact on muscle and bone health, and can lead to conditions including osteoporosis and rickets.

“We know vitamin D deficiency can weaken the muscular and skeletal systems, but until now, little was known about the relationship of vitamin D with muscle power and force,” said Dr. Kate Ward, Ph.D., of the University of Manchester in the U.K., and lead author of the study. “Our study found that vitamin D is positively related to muscle power, force, velocity and jump height in adolescent girls.”

For this study, researchers followed 99 adolescent girls between the ages of 12 and 14 years. Dr. Ward and her colleagues took blood samples to measure the girls’ serum levels of vitamin D. Many of these girls were found to have low levels of vitamin D despite not presenting any symptoms.

Researchers used a novel outcome measure called jumping mechanography to measure muscle power and force. Jumping mechanography derives power and force measurements from a subject’s performance in a series of jumping activities. Dr. Ward says this method of testing is ideal as the muscles required to jump are those most often affected in subjects with vitamin D deficiency. Girls without vitamin D deficiency performed significantly better in these tests.

“Vitamin D affects the various ways muscles work and we’ve seen from this study that there may be no visible symptoms of vitamin D deficiency,” said Dr. Ward. “Further studies are needed to address this problem and determine the necessary levels of vitamin D for a healthy muscle system.”

Obese people with asthma have nearly 5 times greater risk of hospitalization for asthma

First study to control for risk factors of smoking, medication, gastroesophageal reflux and demographics

September 4, 2008 (Portland, Ore.) – Obese people who have asthma are nearly five times more likely to be hospitalized for the condition than non-obese people with asthma, according to a Kaiser Permanente study published in the September issue of the Journal of Allergy and Clinical Immunology.

This is the first study to control for the risk factors – smoking, use of oral or inhaled corticosteroid medications, gastroesophageal reflux disorder, and demographics – that might explain the obesity-asthma association. Previous studies have shown that obese people are more likely to suffer asthma than non-obese people, and that obese patients often have more severe asthma than their non-obese counterparts.

More than 20 million Americans have been diagnosed with asthma. Nearly a third of adults with asthma are also obese, according to researchers. The Centers for Disease Control and Prevention defines obesity as having a Body Mass Index of 30 or higher (http://www.cdc.gov/nccdphp/dnpa/obesity/defining.htm)

Researchers at Kaiser Permanente Center for Health Research in Portland, Ore., and the Kaiser Permanente Institute for Health Research in Denver surveyed 1,113 patients in Oregon, Washington, and Colorado, age 35 and older, who have persistent asthma. The researchers asked the patients about their weight, height, smoking habits, other illnesses, treatment and their asthma-specific quality of life, asthma control and asthma-related hospitalizations.

“The big finding here is that even after adjusting for risk factors, obese adults were nearly five times more likely to be hospitalized for their asthma,” said study lead author David M. Mosen, Ph.D., MPH, of the Kaiser Permanente Center for Health Research. “Given that nearly 30 percent of our country is obese, this study is yet another example of the long-term dangers of obesity, along with heart disease, diabetes, stroke and dementia.”

The study uncovered these findings:

  • Obese people with asthma had significantly worse asthma control, lower asthma-related quality of life, and had 4.6 times higher risk for asthma-related hospitalizations than non-obese asthmatics
  • Obese people with asthma were younger and less educated than non-obese people with asthma
  • Obese people with asthma used more oral corticosteroids
  • Obese people with asthma had a higher incidence of gastroesophageal reflux disorder.

 

“The take-home message of this study for clinicians is that obese people with asthma need to be followed more carefully because it’s harder to control their asthma, so they are more likely to end up in the hospital,” said study co-author Dr. Michael Schatz, Chief of Allergy at Kaiser Permanente San Diego Medical Center. “My advice for obese asthmatics is: be vigilant to keep your asthma symptoms in check, make sure you know what to do when your symptoms worsen, and do whatever you can to lose weight.”

Source: Kaiser Permanente

How gastric bypass rapidly reverses diabetes symptoms

A report in the September Cell Metabolism, a publication of Cell Press, offers new evidence to explain why those who undergo gastric bypass surgery often show greater control of their diabetes symptoms within days. It also helps to explain why lap-band surgery doesn’t offer the same instant gratification. By studying mice that have undergone both procedures, the researchers show that changes in the intestine are the key.

In addition to removing about two-thirds of the stomach, gastric bypass in effect produces a “double intestine,” said Gilles Mithieux of Institut National de la Sante et de la Recherche Medicale in France. The portion closest to the stomach is taken out of the loop so that it receives no nutrients. The segment normally farther down is then attached directly to the stomach, where it receives all the nutrients coming in.

In both cases, those positional changes ramp up production of blood sugar by the small intestine, Mithieux said. He noted that fasting normally induces blood sugar production by the upper small intestine. By placing the lower small intestine, which doesn’t normally produce much glucose, in close proximity to the stomach, it starts to act more like the upper portion.

That blood sugar synthesized in the intestine pours into the portal vein (a large vein that carries blood from the digestive tract to the liver) where it sends a signal to the brain, he and his colleagues earlier found. “The walls of the portal vein system detect the glucose and inform the brain,” he said. “It’s an important signal for decreasing hunger.”

They now find an important new element of glucose production by the intestine. It also increases insulin sensitivity and lowers blood sugar, improving the symptoms of diabetes. Mithieux said that’s in part because glucose production by the intestine lowers glucose production by the liver, which accounts for a much greater overall proportion of blood sugar synthesis. These metabolic changes take place within days of surgery, well before any weight loss takes place.

While gastric banding, in which a prosthetic band is placed around the upper stomach, works for weight loss, it doesn’t affect the intestine at all and lacks the immediate metabolic benefits of bypass, they report.

Further evidence for the mechanism involved came from studies of mice lacking GLUT-2, a glucose transporter required for glucose sensing in the portal vein. Gastric bypass lost its insulin-sensitizing benefits in those GLUT-2-deficient mice. Similarly, mice whose portal veins had lost their nerve supply also stopped responding to the surgical procedure.

The bottomline, according to Mithieux: the intestine deserves more respect. “Up to now, the intestine had been considered like a machine to assimilate nutrients. We’ve now begun to realize that it is a complex endocrine organ” with particular importance when it comes to glucose metabolism.

As for what patients weighing gastric bypass versus lap-band surgery should do, Mithieux recommends they talk to their doctors about the possible benefits and risks of both procedures. The new findings do support the notion that gastric bypass may be an effective treatment for diabetes in obese patients. It might even have potential for people who are diabetic, whether they are obese or not, he said.

Source: Cell Press

Issues on cholesterol: Diet, statins and genetics

Conversely, lifestyle, diabetes, dyslipidemia, cigarette smoking and hypertension contribute to most of the population-attributable risk in the large, international INTERHEART study of acute myocardial infarction (heart attacks). The identification of single gene disorders may pave the way to a better understanding of complex metabolic pathways. Understanding the genes that regulate high density lipoprotein (HDL) metabolism may lead to novel therapeutic approaches. This has been emphasized by two therapeutic approaches for the treatment of CAD:

     

  • The infusion of apo AI containing proteoliposomes, using wild-type or a mutant form of apo AI, apo AIMilano, in patients with acute coronary syndromes;

     

     

  • The long-term treatment of subjects with low HDL-C with the cholesteryl ester transfer protein (CETP) inhibitor Torcertapib. While Torcetrapib proved to have off-target toxic effects, two other CETP inhibitors (Anacetrapib and Delcetrapib) are being tested clinically. Experimentally, however, CETP inhibitors may not reduce atherosclerosis

     

Novel therapeutic approaches using agonists of the LxR/RxR pathway to up-regulate the ABCA1 transporter, or the transcriptional regulation of apo AI, are being explored.

 

Plasma (or serum) level of HDL-C is a continuous and graded negative cardiovascular risk factor. Most international CAD prevention guidelines define HDL-C as a categorical risk factor and the absolute level of HDL-C is used in a multivariate model to predict cardiovascular risk and determine the need and intensity of preventive therapies. A low HDL-C is considered a diagnostic criterion for the metabolic syndrome.

To underlie the importance of plasma lipoproteins in the pathogenesis of CAD and acute myocardial infarction, the largest case-control study of myocardial infarction (INTERHEART) has shown that the apo B/apo AI ratio (respectively an index of atherogenic lipoproteins and protective lipoproteins) accounts for approximately half (49%) of the population-attributable risk of acute myocardial infarction. The prevalence of a low HDL-C in patients with CAD has been examined in several case-control and prospective studies. It is estimated that approximately 40% of patients with premature CAD have a low HDL-C and this represents the most common lipoprotein disorder in patients with CAD. Most patients with a low HDL-C have multiple cardiovascular risk factors and features of the metabolic syndrome, with obesity (predominantly abdominal), elevated plasma triglyceride levels, high blood pressure and hyperglycemia, insulin resistance or diabetes. Despite the strong association between metabolic disorders and HDL-C, plasma levels of HDL-C are strongly genetically determined. Experimental evidence shows that the atheroprotective effects of HDL are pleiotropic and extend beyond removing cholesterol from lipid-laden macrophages in the atherosclerotic plaque. HDL are known to have anti-inflammatory effects, to prevent oxidation of low-density lipoproteins (LDL), possess anti-thrombotic properties, modulate vasomotor tone and may improve endothelial cell survival (by preventing apoptosis), migration and proliferation. Nonetheless, the major cardio-protective effect of HDL has been attributed to its key role in reverse cholesterol transport, a process in which cholesterol from peripheral tissues such as foam cells is selectively returned to the liver for excretion in the bile. Mutations in any of the proteins regulating this complex metabolic pathway may potentially decrease HDL-C levels and accelerate CAD.

 

Mutations or polymorphisms in several genes have been associated with altered plasma HDL-C levels. Mutations in the cholesteryl ester transfer protein (CETP) gene are associated with increases in HDL-C whereas mutations in the apolipoprotein (apo) AI gene (the major apolipoprotein of HDL particles), or the lecithin:cholesterol acyl transferase (LCAT) gene cause a low HDL-C. Of the approximately 46 mutations affecting the structure of apo AI, not all are associated with CAD. Mutations in the lipoprotein lipase (LPL) and hepatic lipase (HL) genes also affect HDL-C levels. The identification of the ATP binding cassette A1 gene (ABCA1) as the cause of Tangier disease and familial HDL deficiency has led to a better understanding of the role of cellular cholesterol and phospholipid transport in the metabolism of nascent HDL particles. Based upon the analysis of a selected group of subjects, we estimate that approximately 10-20% of subjects with severe HDL deficiency have mutations of the ABCA1 gene. Other genes have been found in animal models to have a profound impact on HDL-C levels, although no human counterpart disorders have yet been identified.

 

To examine the genetic contribution to the determination of HDL-C levels, there have been at least nine published studies in twins and 14 family studies. Estimates for the heritability of plasma HDL-C levels varies between 0.24 to 0.83 and is most often quoted as approximately 0.5.

 

The inverse epidemiological association between serum levels of HDL-C and risk of CAD is graded and has been validated in multiple studies. However, there is remaining controversy whether a low HDL-C should not predominantly be considered a marker of poor lifestyle (obesity, lack of exercise, hypertriglyceridemia, diet, etc.), rather than a primary causal agent for atherosclerosis in the majority of the population. Specific mutations in genes affecting HDL-C levels have had considerable discordant effects on CAD risk. For instance, mutations in the apo AI gene affecting HDL-C levels can be strongly associated with premature CAD, but apo AIMilano and apo AIParis are notable exceptions. Mutations in the LCAT gene cause a marked decreased level of HDL-C but are not considered to be associated with CAD. While loss-of-function mutations in the CETP gene cause an elevated HDL-C, cardiovascular risk does not seem decreased and may in fact be increased. Mutations in ABCA1 are associated with very low HDL-C and increase cardiovascular risk 3.5 fold in one study, but more recent data from the Copenhagen Heart Study suggests that ABCA1 mutations are not associated with increase cardiovascular risk, despite being associated with a low HDL-C. Important questions therefore remain which genetic forms of HDL deficiency confer cardiovascular risk. This has implications for the identification and treatment of patients with HDL deficiency. It remains to be determined whether a genetic form of HDL deficiency confers cardiovascular risk.

Source: European Society of Cardiology

 

Genetics of HDL and risk of cardiovascular disease

Heritability of HDL-C

Genes that affect HDL-C levels

Epidemiology of HDL and risk of coronary artery disease CAD risk

Heavy breathing — an obscure link in asthma and obesity

There is a strong link between obesity and asthma and as the prevalence of both conditions has been increasing steadily, epidemiologists have speculated that there is an underlying condition that connects the two. But one long-suspected link, the systemic inflammation associated with obesity, has been ruled out by a recent New Zealand study that found no evidence of its involvement.

“We were disappointed not to find a ‘smoking gun’ that would explain the common association between obesity and asthma,” said lead researcher, D. Robin Taylor, M.D., of the University of Otago in New Zealand. “However, this research points us to other possibilities that future research should examine.”

The results were reported in the first issue for September of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.

“We hypothesized that the low-grade systemic inflammation present in obesity would augment the inflammation of asthma (a synergistic effect),” wrote Dr. Taylor. “Or alternatively, that the inflammation of obesity might affect the airways independently (an additive effect), perhaps resulting in mixed airway inflammation.”

In order to determine if there was indeed an interaction between systemic and local inflammation, the researchers recruited 79 women—20 who were obese with asthma, 19 who were of a normal weight with asthma, 20 who were obese but who did not have asthma and 20 controls.

Asthmatics were told to stop using their anti-inflammatory inhaler treatment to avoid confounding effects until “loss of control.” After the withdrawal period of four weeks, subjects underwent blood tests and tests for biomarkers of systemic and airway inflammation, such as C-reactive protein (CRP) and cytokines in blood and inflammatory cells and cytokines in sputum. Those that are known to be relevant in both obesity and asthma were chosen. The researchers then analyzed for interactions between systemic and airway-specific markers of inflammation.

“What we found was that although inflammatory cells and other biomarkers of inflammation were increased, there was no significant interaction demonstrated between obesity and asthma,” said Dr. Taylor.

Although their inflammation hypothesis was not supported by their results, Dr. Taylor points out that it does provide valuable direction for future research. “This does not change the fact that there is a well-established link between asthma and obesity. Sometimes a negative result is important, and the results add to our body of knowledge regarding the obesity-asthma link. Now we need to look in other directions for the answers.”

Animal studies suggest that changes in innate immunity may occur with obesity. “We did not look at this in our patients. Given that asthma is immunologically driven, this is a potential avenue for further research,” said Dr. Taylor. “Alternatively, it may be that dynamic changes in lung function that occur with episodes of asthma are different with excess body weight.”

Whatever the link is, uncovering it will have important clinical implications. “Obese patients with asthma are more difficult to treat because their response to bronchoconstriction is exaggerated and gives the impression that the asthma is worse,” said Dr. Taylor. “They may well have worse symptoms, but not as a result of underlying airway inflammation. Still, the typical response is often to increase their inhaled anti-inflammatory therapy. This is unlikely to provide the answer and may even do harm. The answer lies in dealing with the obesity itself.”

Source: American Thoracic Society